{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T21:55:21Z","timestamp":1789768521675,"version":"4.0.1"},"reference-count":43,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T00:00:00Z","timestamp":1675641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070599"],"award-info":[{"award-number":["82070599"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82000545"],"award-info":[{"award-number":["82000545"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Bile components play a critical role in maintaining gut microbiota homeostasis. In cholestasis, bile secretion is impaired, leading to liver injury. However, it remains to be elucidated whether gut microbiota plays a role in cholestatic liver injury. Here, we performed a sham operation and bile duct ligation (BDL) in antibiotic-induced microbiome depleted (AIMD) mice and assessed liver injury and fecal microbiota composition in these mice. Significant reductions in gut microbiota richness and diversity were found in AIMD-sham mice when compared to sham controls. Three-day BDL leads to great elevation of plasma ALT, ALP, total bile acids, and bilirubin where reduced diversity of the gut microbiota was also found. AIMD further aggravated cholestatic liver injury evidenced by significantly higher levels of plasma ALT and ALP, associated with further reduced diversity and increased Gram-negative bacteria in gut microbiota. Further analyses revealed increased levels of LPS in the plasma of AIMD-BDL mice where elevated expression of inflammatory genes and decreased expression of hepatic detoxification enzymes were also found in liver when compared to the BDL group. These findings indicate that gut microbiota plays a critical role in cholestatic liver injury. Maintaining its homeostasis may alleviate liver injury in patients with cholestasis.<\/jats:p>","DOI":"10.3390\/ijms24043180","type":"journal-article","created":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T03:34:30Z","timestamp":1675654470000},"page":"3180","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Gut Microbiota Deficiency Exacerbates Liver Injury in Bile Duct Ligated Mice via Inflammation and Lipid Metabolism"],"prefix":"10.3390","volume":"24","author":[{"given":"Xueqian","family":"Zhou","sequence":"first","affiliation":[{"name":"Cholestatic Liver Diseases Center, Department of Gastroenterology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3892-7464","authenticated-orcid":false,"given":"Xiaoxun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Cholestatic Liver Diseases Center, Department of Gastroenterology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Cholestatic Liver Diseases Center, Department of Gastroenterology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangjun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Cholestatic Liver Diseases Center, Department of Gastroenterology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Qiu","sequence":"additional","affiliation":[{"name":"Cholestatic Liver Diseases Center, Department of Gastroenterology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunwei","family":"Song","sequence":"additional","affiliation":[{"name":"Cholestatic Liver Diseases Center, Department of Gastroenterology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Chai","sequence":"additional","affiliation":[{"name":"Cholestatic Liver Diseases Center, Department of Gastroenterology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiying","family":"Cai","sequence":"additional","affiliation":[{"name":"The Liver Center, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wensheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Cholestatic Liver Diseases Center, Department of Gastroenterology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1016\/j.jhep.2015.08.001","article-title":"Implications of microbiota and bile acid in liver injury and regeneration","volume":"63","author":"Liu","year":"2015","journal-title":"J. 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